Odense Child Cohort Study Research Articles

Maternal selenium deficiency during pregnancy in association with autism and ADHD traits in children: The Odense Child Cohort

BackgroundSelenoproteins regulate pathways controlling neurodevelopment, e.g., redox signaling and thyroid hormone metabolism. However, studies investigating maternal selenium in relation to child neurodevelopmental disorders are scarce. Methods719 mother-child pairs from the prospective population-based Odense Child Cohort study in Denmark were included. Three selenium biomarkers, i.e. concentrations of serum selenium, selenoprotein P (SELENOP), and activity of glutathione peroxidase 3 (GPX3), along with serum copper, zinc and iron were measured in early third trimester (at 28.9+/-0.8 weeks of pregnancy). ADHD and ASD traits in children were assessed systematically using the established Child Behaviour Checklist at 5 years of age, based on a Danish reference cohort with cut-off at 90th percentile. Multivariable regression models adjusted for biologically relevant confounders were applied. Results155 of 719 (21.6 %) children had ASD traits and 59 of 719 (8.2 %) children had traits of ADHD at 5 years of age. In crude and adjusted models, all three selenium biomarkers associated inversely with ADHD traits. For ADHD, fully adjusted OR for 10 μg/L increment in selenium was 0.76 (95 % CI 0.60, 0.94), for one mg/L increment in SELENOP was 0.73 (0.56, 0.95), and for 10 U/L increment in GPx3 was 0.93 (0.87,1.00). Maternal total selenium was inversely associated with child ASD traits, OR per 10 μg/L increment was 0.85 (0.74, 0,98). SELENOP and GPx3 were not associated with ASD traits. The associations were specific to selenium, as other trace elements such as copper, zinc, or iron were not associated with the outcomes. ConclusionsThe results provide coherent evidence for selenium deficiency as a risk factor for ADHD and ASD traits in an environment with borderline supply, the causality of which should be elucidated in a randomized controlled trial.

Thyroid autoimmunity in euthyroid pregnant women is associated with slower productive language acquisition: the Odense child cohort study.

Maternal thyroid autoimmunity and thyroid function in early pregnancy may impact fetal neurodevelopment. We aimed to investigate how thyroid autoimmunity and thyroid function in early pregnancy were associated with language acquisition in offspring at 12-36 months of age. This study was embedded in the prospective Odense child cohort. Mother-child dyads were excluded in case of maternal intake of thyroid medication during pregnancy. The parents completed MacArthur-Bates Communicative Development Inventories (MB-CDI) every third month to assess their offspring's productive vocabulary. All completed reports for each child were included in the analyses. Logistic growth curve models evaluated associations between MB-CDI scores and levels of maternal thyroid peroxidase antibodies (TPOAb), free thyroxine (FT4), and thyrotropin, respectively, measured in early pregnancy (median gestational week 12). All models were stratified by offspring sex and adjusted for maternal age, education, pre-pregnancy body mass index, parity, breastfeeding, and offspring age. The study included 735 mother-child dyads. Children born to mothers with TPOAb ≥11 kIU/L, opposed to TPOAb <11 kIU/L, had a lower probability of producing words at age 18-36 months for girls (OR = 0.78, P < 0.001) and 33-36 months for boys (OR = 0.83, P < 0.001). The probability of producing words was higher in girls at 30-36 months of age with low-normal maternal FT4 vs high-normal FT4 (OR = 0.60, P < 0.001), and a similar trend was seen in boys. Results were ambiguous for thyrotropin. In women without known thyroid disease, TPOAb positivity in early pregnancy was negatively associated with productive vocabulary acquisition in girls and boys. This association was not mediated by a decreased thyroid function, as low-normal maternal FT4, unexpectedly, indicated better vocabulary acquisition. Our results support that maternal thyroid autoimmunity per se may affect fetal neurodevelopment.

Serum selenium, selenoprotein P, and glutathione peroxidase 3 during early and late pregnancy in association with gestational diabetes mellitus: Prospective Odense Child Cohort

BackgroundDiet is an important modifiable risk factor for gestational diabetes mellitus (GDM) and its related complications; however, the role of essential micronutrients such as selenium (Se), particularly in populations with low Se intake, is inconclusive. ObjectivesThe aim was to investigate the association of 3 established biomarkers of Se status with GDM, gestational glucose metabolism, and large for gestational-age offspring. MethodsThis study included 1346 pregnant females with 2294 serum samples from the prospective, population-based Odense Child Cohort study, Denmark. Serum Se, selenoprotein P (SELENOP) concentrations, and glutathione peroxidase 3 (GPX3) activity were measured in early and late pregnancy, and fasting glucose and insulin assessments in late pregnancy. Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) was calculated, and the GDM definition was according to the WHO 2013 threshold of fasting venous plasma glucose of ≥5.1 mmol/L. A subcohort underwent an oral glucose tolerance test. Regression models adjusted for various confounders quantified dose-dependent associations. ResultsSe and SELENOP declined during pregnancy. There were dose-dependent inverse associations of early GPX3 with late pregnancy GDM (WHO 2013), fasting glucose, insulin, HOMA-IR, and 2 h glucose. The odds ratio (OR) of GDM was 0.33 (95% CI: 0.16, 0.65) for 1 log-scale-increment in early GPX3 activity. Late pregnancy GPX3 and SELENOP were inversely associated with GDM and HOMA-IR; the OR of GDM was 0.21 (95% CI: 0.12, 0.38) and 0.52 (95% CI: 0.35, 0.77), for 1 log-scale-increment of GPX3 and SELENOP, respectively. A decline in Se biomarkers during pregnancy was associated with a higher risk of GDM and higher HOMA-IR. Low GPX3 activity in late pregnancy was associated with a higher risk of large for gestational-age offspring, partly (∼20%) mediated by fasting glucose concentrations (P = 0.006). ConclusionsLow serum Se in pregnancy, particularly GPX3 activity, is independently associated with risk of GDM and large for gestational age. Offering Se status assessment in pregnancy identifies females at high risk for GDM who may benefit from Se substitution.

The association between maternal thyroid function and language acquisition in offspring aged 12 to 37 months: an odense child cohort study

The association between maternal thyroid function and language acquisition in offspring aged 12 to 37 months: an odense child cohort study

Vitamin D status in pregnancy and childhood associates with intelligence quotient at age 7 years: An Odense child cohort study.

Animal studies indicate a key role for vitamin D in brain development and function, but observational studies in humans only suggests a borderline positive association between prenatal vitamin D exposure and cognitive development in the offspring. Knowledge gaps include insights in exposure time window and differences by sex for the association. We aimed to investigate the association between blood concentrations of serum 25-hydroxyvitamin D measured at four different time points and intelligence quotient score at the age of 7 years, including analyses spilt by child sex. In Odense child cohort, we included 1404 mother-child pairs with serum 25-hydroxyvitamin D data from early pregnancy to age 7 years. Full-scale intelligence quotient was assessed with Wechsler Intelligence Scale for Children - fifth edition. Associations were adjusted for maternal education, pre-pregnancy body mass index, gestational age, sex and head circumference. Subanalyses stratified by sex were performed. The median (interquartile range) serum 25-hydroxyvitamin D in cord was 45.88 (31.15-61.08) nmol/L; early pregnancy, 66.45 (51.29-78.74); late pregnancy, 79.13 (59.69-97.31); 7 years, 66.29 (53.45-80.23) nmol/L. The mean (standard deviation) full-scale intelligence quotient was 99.44 (11.98). In adjusted analyses, cord serum 25-hydroxyvitamin D < 50 nmol/L was associated with 2.2 points lower full-scale intelligence quotient compared to the reference (50-75 nmol/L) in boys, β = -2.2; 95% confidence interval = [-4.3, -0.1], p = 0.039. The same association with full-scale intelligence quotient was found for early pregnancy serum 25-hydroxyvitamin D, β = -2.5 [-4.6, -0.3], p = 0.025, primarily driven by an association in boys, β = -4.0 [-7.2, -0.8], p = 0.015; and for serum 25-hydroxyvitamin D at 7 years in girls, β = -3.0 [-6.0, -0.1], p = 0.042. In this cohort, serum 25-hydroxyvitamin D < 50 nmol/L in both early gestation and cord blood in boys and current serum 25-hydroxyvitamin D < 50 nmol/L in girls were independent risk factors for two to four points lower full-scale intelligence quotient at the age of 7 years. Vulnerability to hypovitaminosis D, especially in pregnancy, may relate to child sex.

Early pregnancy vitamin D status is associated with blood pressure in children: an Odense Child Cohort study

ABSTRACTBackgroundBlood pressure in childhood tracks into later life. Vitamin D status in adults is associated with blood pressure, but the impact of vitamin D status in pregnancy and childhood on blood pressure still needs investigation.ObjectiveWe investigated whether fetal rather than current vitamin D status is associated with blood pressure in children.MethodsIn a prospective observational study within the population-based Odense Child Cohort (OCC), we examined serum 25-hydroxyvitamin D2+3 [s-25(OH)D] in early and late pregnancy, cord blood, and at 5 y age, and the associations with systolic and diastolic blood pressure (SBP/DBP) in the 5-y-old children (n = 1,677). Multiple regression models were adjusted for maternal country of origin, parity, smoking during pregnancy, 5-y height, and weight. Two-stage mixed effect modeling was performed, integrating all s-25(OH)D data from pregnancy and cord blood.ResultsThe median (IQR) s-25(OH)D in early pregnancy, late pregnancy, the umbilical cord, and at 5 y was 65.5 (50.7–78.5), 78.5 (60.3– 95.8), 45.4 (31.1– 60.7), and 71.9 (54.6– 86.5) nmol/L, respectively. The mean ±SD 5-y SBP/DBP was 101.0/63.8 (7.1/5.9) mmHg. In adjusted analyses, a 10 nmol/L increase of s-25(OH)D in early pregnancy associated with a 0.3/0.2 mmHg lower SBP/DBP at 5 y (P < 0.05). Optimal s-25(OH)D (>75 nmol/L) in early pregnancy was associated with lower 5-y SBP and DBP, β (95% CI) −1.45 (−2.6, −0.3), and −0.97 (−1.9, −0.1), compared with reference s-25(OH)D (50-74.9 nmol/L). Two-stage analysis combining early pregnancy, late pregnancy, and cord s-25(OH)D data showed an inverse association with 5-y SBP and DBP for boys (P < 0.025) with significant sex-difference for DBP (Pinteraction = 0.004). No associations were found between s-25(OH)D and 5-y BP above the 90th percentile.ConclusionEarly pregnancy s-25(OH)D concentrations, especially >75 nmol/L, were inversely associated with 5-y blood pressure in the offspring. A novel identified protective effect of optimal vitamin D levels in early pregnancy on offspring BP is suggested.

Health anxiety symptoms in Danish children during the COVID-19 pandemic: An Odense Child Cohort study

Health anxiety symptoms in Danish children during the COVID-19 pandemic: An Odense Child Cohort study

Vitamin D status and tooth enamel hypomineralization are not associated in 4-y-old children: An Odense Child Cohort study

Early fetal stages of tooth development are vitamin D-dependent, suggesting an impact of vitamin D status in pregnancy on tooth mineralization in human populations. We examined the association between pregnancy and cord serum 25-hydroxyvitamin D (s-25(OH)D) and hypomineralization of the second primary molars (HSPM) in the 4-year-old children in the prospective, population-based Odense Child Cohort, Denmark. S-25(OH)D was measured in early pregnancy (<20 weeks, n = 753); late pregnancy (≥20 weeks, n = 841); and in umbilical cord blood (n = 1,241) using liquid chromatography-tandem mass spectrometry. HSPM was scored using modified European Academy of Paediatric Dentistry judgment criteria. The median [Q1;Q3] s-25(OH)D was 65.0 [49.4;78.0], 79.2 [60.4;95.8], and 45.1 [31.2;60.5] nmol/L in early pregnancy, late pregnancy, and cord blood, respectively. The prevalence of HSPM was 54.7%; creamy/white demarcated opacities 79.5%; yellowish/brownish demarcated opacities 14.9%; post-eruptive breakdown 5.2%; atypical restoration 0.4%. No univariate or adjusted associations with HSPM were detected for pregnancy or cord s-25(OH)D as a continuous variable or categorized into quartiles or routine clinical cut-offs, or when classifying HSPM by severity. In exploratory multiple regression analysis, HSPM was inversely associated with the length of gestation, adjusted odds ratio (aOR) 0.82 (95% C.I 0.74–0.92, p < 0.001), and directly associated with maternal education, aOR 1.57 (95% C.I 1.18–2.08, p = 0.002). In a population with relatively high s-25(OH)D concentrations and generally healthy mothers and children, pregnancy and cord blood vitamin D status was not associated with HSPM. The associations between HSPM and shorter gestational length and higher maternal education warrant further study.

Health anxiety symptoms in Danish children during the first lockdown period of the COVID-19 pandemic: an Odense Child Cohort study

Purpose The coronavirus disease 2019 (COVID-19) pandemic has a severe impact on the general population. During the pandemic, children may develop emotional and psychological symptoms, including increased worries about health and illness, known as health anxiety symptoms (HASs). We aimed to explore HAS in 7–9-year-old children from the Danish Odense Child Cohort (OCC) during the first COVID-19 lockdown period in Denmark, and to examine associations with potential risk factors. Material and methods OCC is a cohort of children born between 2010 and 2012, which originally recruited 2874 of 6707 pregnancies (43%). Among the current OCC population of 2430 singleton children, 994 participated in this study (response rate 40%). Children and their parents filled out questionnaires about child HAS, family exposure to COVID-19 infection and parental HAS. Adjusted odds ratios (aORs) were calculated between high score child HAS (≥90th percentile) and covariates by use of logistic regression. Results Most children (n = 686, 69%) reported few worries about their health. Children reporting high score HAS also had higher levels of internalizing symptoms at age 5; aOR 2.15 (1.20;3.85), p = .010, and higher levels of maternal and paternal HAS; aOR 2.40 (1.44;3.97), p = .001, and 2.00 (1.10;3.65), p = .023, whereas no association with child sex or familial exposure to COVID-19 was detected (n = 65, 6.5%). Conclusions High score child HAS during the first lockdown period of the COVID-19 pandemic was not associated with family exposure to COVID-19 infection, but to being a more anxious child a priori and to HAS in parents.

Bone mineral density at age 7 years does not associate with adherence to vitamin D supplementation guidelines in infancy or vitamin D status in pregnancy and childhood: an Odense Child Cohort study.

Vitamin D supplementation in infancy is recommended to prevent rickets. At the population level, its effects on bone mineralisation are largely unknown. We aimed to explore whether adherence to national vitamin D supplementation guidelines (10 µg/d up to the age of 2 years), supplementation at the ages of 5 and 7 years, and serum 25-hydroxyvitamin D (s-25(OH)D) at various time points associated with bone mineral density (BMD) at the age of 7 years in the Odense Child Cohort, Denmark (n 1194). High adherence was defined as supplementation with 10 µg of vitamin D 6-7 times per week during ≥80 % of the observation time. s-25(OH)D was analysed using LC-MS/MS. Total-body-less-head (TBLH) BMD was measured by dual-energy X-ray absorptiometry. At the median age of 18·1 months, 53·9 % (n 475/881) reported high adherence. The median s-25(OH)D was 64·7, 78·8, 46·0 and 71·8 nmol/l in early pregnancy, late pregnancy, cord blood and at 5 years, respectively. The mean TBLH BMD at the median age of 7·1 years was 0·613 (SD 0·049) g/cm2 (z-score +0·363 (SD 0·824)). In adjusted analyses, vitamin D supplementation up to 18 months, and at 5 and 7 years, was not associated with TBLH BMD. Similarly, no robust associations were found between TBLH BMD and s-25(OH)D at any time point. No associations were found for TBLH bone mineral concentration or bone area. In this population with relatively high s-25(OH)D concentrations, no consistent associations were found between adherence to vitamin D supplementation recommendations or vitamin D status in pregnancy or childhood, and bone mineralisation at the age of 7 years.

Prenatal Exposures to Perfluoroalkyl Acids and Associations with Markers of Adiposity and Plasma Lipids in Infancy: An Odense Child Cohort Study.

Background:Perfluoroalkyl acids (PFAA) are repellants that cross the placental barrier, enabling interference with fetal programming. Maternal PFAA concentrations have been associated with offspring obesity and dyslipidemia in childhood and adulthood, but this association has not been studied in infancy.Objectives:We investigated associations between maternal PFAA concentrations and repeated markers of adiposity and lipid metabolism in infancy.Methods:In the prospective Odense Child Cohort, maternal pregnancy serum concentrations of five PFAA: Perfluorohexane sulfonic acid (PFHxS), perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), and perfluorodecanoic acid (PFDA) were measured in 649 women. Offspring were examined at birth () and at 3 months () and 18 months () of age. Total cholesterol, LDL, HDL, and triglyceride were evaluated at 3 months () and 18 months () of age. Mixed effects linear regression models estimated associations between PFAA and standardized (SDS) body mass index (BMI), ponderal index, and waist circumference. Associations between PFAA and body fat% (BF%) and plasma lipids SDS at 3 months and 18 months of age were investigated with linear regression models.Results:PFNA and PFDA were associated with higher BMI SDS [adjusted ; 95% confidence interval (CI): 0.03, 0.49 and ; 95% CI: , 1.19, respectively, for increases] and ponderal index SDS (; 95% CI: 0.13, 0.59 and ; 95% CI: 0.40, 1.64, respectively) at 3 and 18 months of age (pooled) in girls. Corresponding estimates for boys were closer to the null but not significantly different from estimates for girls. In boys and girls (combined), PFNA and PFDA were associated with BF% at age 3 months (for PFDA, ; 95% CI: 0.04, 0.75), and PFDA was associated with total cholesterol SDS at 18 months (; 95% CI: 0.08, 2.03) ().Discussion:Prenatal PFAA were positively associated with longitudinal markers of adiposity and higher total cholesterol in infancy. These findings deserve attention in light of rising rates of childhood overweight conditions and dyslipidemia. https://doi.org/10.1289/EHP5184

Screen-based media use and blood pressure in preschool-aged children: A prospective study in the Odense Child Cohort.

Aims: To examine prospective and cross-sectional associations between screen time and blood pressure (BP) in preschool children. Methods: The Odense Child Cohort study started in January 2010. Children who were born in the municipality of Odense underwent a clinical examination at 3 and 5 years of age and their parents were asked to complete a questionnaire. A total of 628 children were included in the prospective analysis and 964 children were included in two cross-sectional analyses at 5 years of age. Multivariable adjusted linear and logistic regression models were computed to examine prospective and cross-sectional associations between screen time and BP with adjustment for putative confounding factors. Results: No significant prospective association was found between a 2-year change in screen time and systolic BP (0.55 BP percentile change per 1 h increase in screen time, 95% confidence interval (CI) -1.51 to 2.60) and diastolic BP (0.74 BP percentile change per 1 h increase in screen time, 95% CI -1.09 to 2.57). No significant cross-sectional association was observed between screen time (⩽1 h/day, >1-2 h/day, >2 h/day) and the prevalence of high BP at 5 years of age. Exposure to screen time before bedtime 2-5 days/week and ⩾6 days/week was significantly associated with a greater prevalence of high BP compared with screen time before bedtime 0-1 day/week (odds ratios 1.57 (95% CI 1.02-2.42) and 1.82 (95% CI 1.18-2.89), respectively. Conclusions: No prospective association was found between screen time and BP. However, a significant cross-sectional association was found between screen time before bedtime and high BP in preschool children.

Pregnancy or cord 25-hydroxyvitamin D is not associated with measures of body fat or adiposity in children from three months to three years of age. An Odense Child Cohort study

The susceptibility to overweight in adults born during winter season may suggest foetal programming of prenatal vitamin D levels on adiposity. We investigated whether cord or pregnancy serum 25-hydroxyvitamin D (s-25OHD) was associated with infant and child body fat measures in a Danish population-based prospective cohort. In the Odense Child Cohort, 1905 singletons had cord s-25OHD and data on waist circumference (WC), weight, body mass index (BMI), and sum of skin folds (SSF) at median 3.7 months, 18.9 months and three years' age. Early and late pregnancy samples of s-25OHD (mean gestational age 12 and 29 weeks) were chosen as secondary exposures. Multiple linear and logistic regression as well as linear mixed models was applied testing the relation between cord and pregnancy s-25OHD and body fat outcomes and their Z-scores by use of updated national reference populations. Models were adjusted for maternal educational level, maternal ethnicity, pre-gestational BMI and season of birth, a priori stratified by sex. The median [IQR] cord s-25OHD was 45.5 [31.1; 60.9] nmol/L. Cord s-25OHD <50nmol/L was found in 57.5%; values<25nmol/L in 16.3%. The mean Z-scores of body fat measures at all ages were in the range of-0.32 to+0.42. No consistent associations were found between s-25OHD in cord, early pregnancy or late pregnancy and WC, weight, BMI, SSF, or their Z-scores at ages 3.7 months, 18.9 months, or 3 years. Neither did a computed composite outcome (WC, SSF, BMI, or weight >90th vs. ≤90 percentile) associate with cord or pregnancy s-25OHD. Cord or pregnancy s-25OHD was not associated with measures of body fat or adiposity in children up to three years of age. Our data suggested no programming effect of maternal s-25OHD on offspring obesity in a relatively lean and healthy population of mothers.

Blood pressure in 3-year-old girls associates inversely with umbilical cord serum 25-hydroxyvitamin D: an Odense Child Cohort study.

BackgroundLow foetal vitamin D status may be associated with higher blood pressure (BP) in later life.ObjectiveTo examine whether serum 25-hydroxyvitamin D2+3 (s-25OHD) in cord and pregnancy associates with systolic and diastolic BP (SBP; DBP) in children up to 3 years of age.DesignProspective, population-based cohort study.MethodsWe included 1594 singletons from the Odense Child Cohort with available cord s-25OHD and BP data at median age 3.7 months (48% girls), 18.9 months (44% girls) or 3 years (48% girls). Maternal s-25OHD was also assessed at gestational ages 12 and 29 weeks. Multiple regression models were stratified by sex a priori and adjusted for maternal educational level, season of birth and child height, weight and age.ResultsIn 3-year-old girls, SBP decreased with −0.7 mmHg (95% CI −1.1; −0.3, P = 0.001) and DBP with −0.4 mmHg (95% CI −0.7; −0.1, P = 0.016) for every 10 nmol/L increase in cord s-25OHD in adjusted analyses. Moreover, the adjusted odds of having SBP >90th percentile were reduced by 30% for every 10 nmol/L increase in cord s-25OHD (P = 0.004) and by 64% for cord s-25OHD above the median 45.1 nmol/L (P = 0.02). Similar findings were observed between pregnancy s-25OHD and 3-year SBP, cord s-25OHD and SBP at 18.9 months, and cord s-25OHD and DBP at 3 years. No consistent associations were observed between s-25OHD and BP in boys.ConclusionCord s-25OHD was inversely associated with SBP and DBP in young girls, but not in boys. Higher vitamin D status in foetal life may modulate BP in young girls. The sex difference remains unexplained.

Prediction of birth weight small for gestational age with and without preeclampsia by angiogenic markers: an Odense Child Cohort study

Purpose: To investigate the predictive performance of placental growth factor (PlGF) and soluble FMS-like kinase 1 (sFlt-1) on birth weight and small for gestational age (SGA), in a large, population-based cohort.Methods: Women enrolled in the population-based, prospective Odense Child Cohort Study with early (GA < 20 weeks) and/or late (≥20 weeks) pregnancy blood samples (n = 1937) were included. The association between log-transformed values of the biomarkers and birth weight Z-score was studied using multivariate regression models. The prediction of SGA overall, and in women developing preeclampsia, by biomarkers was evaluated using receiver operating characteristic analyses.Results: No substantial associations between early pregnancy biomarkers and SGA were seen. PlGF measured in late pregnancy demonstrated the strongest association with birth weight Z-score (adjusted β-coefficient = 0.43 [95%CI = 0.35; 0.50]). The area under curve (AUC) for predicting SGA was higher for sFlt-1/PlGF compared to sFlt-1 (0.74 versus 0.63, p = .006) and reached excellent prediction for SGA after preeclampsia (AUC 0.94). Optimal sFlt-1/PlGF ratio cut-offs had higher negative predictive value (NPV) and positive predictive value (PPV) for SGA (cut-off > 5.0; NPV = 99.1%, PPV = 5.4%) compared to each marker individually.Conclusion: The sFlt-1/PlGF ratio is a potential predictor of SGA in population-based screening, particularly when preeclampsia is also present.

151. Aldosterone as independent predictor of placental and birth weights: Odense Child Cohort study

Introduction Aldosterone is involved in plasma volume expansion and its levels, along with the levels of other members of the renin-angiotensin-aldosterone system (RAAS), are increased in healthy pregnancy. Aldosterone appears to contribute to an optimal fetal development by enhancing placental growth factor (PlGF) expression and trophoblast cell proliferation. In contrast to normal pregnancy, aldosterone is suppressed in preeclampsia. Hypothesis Aldosterone independently contributes to placental and fetal growth. Methods The project is based on data from the Odense Child Cohort, a prospective population-based study from the Municipality of Odense, Denmark, currently with 2500 active families. The participants were recruited between 2010 and 2012. To analyze plasma aldosterone levels and urinary aldosterone excretion (UAldoV), we used a subsample of 637 urine samples (24-h collections) from gestational week 28. Plasma aldosterone and UAldoV were determined by a commercially available ELISA. Predictive values of aldosterone were assessed by multiple regression analysis. Primary outcomes were placental weight (PW) and gestational age-adjusted birth weight Z-score (BW sds). Results UAldoV, but not plasma aldosterone concentration, independently contributed to PW and BW sds (adjusted β coefficients ± SEM: 3.21 ± 1.51, p Discussion At 28 weeks of gestation, 24-h urinary aldosterone excretion was an independent predictor of placental and birth weights. In perspective, aldosterone could be a candidate biomarker for future screening and monitoring programs of high-risk pregnancies. Our findings support the physiological role for aldosterone and likely NaCl conservation for normal pregnancy. Mineralocorticoid supplementation could be considered for pregnancies with high risk for IUGR in order to achieve elevated levels of mineralocorticoids and thus benefit placental and fetal development.

A novel inverse association between cord 25-hydroxyvitamin D and leg length in boys up to three years. An Odense Child Cohort study.

Background and aimLong standing vitamin D deficiency in children causes rickets with growth impairment. We investigated whether sub-ischial leg length (SLL) is shorter, and cephalo-caudal length:length (CCL:L) ratio and sitting height:height (SH:H) ratio larger, with lower cord s-25-hydroxyvitamin D (25OHD) in the population-based prospective Odense Child Cohort, Denmark.MethodsWe included healthy singletons born to term with available measures of cord 25OHD and anthropometrics up to three years’ age. Linear regression was stratified by sex a priori and adjusted for maternal ethnicity, pre-pregnancy body mass index and smoking during pregnancy, season of blood sampling and child age.ResultsMedian (IQR) cord 25OHD was 48.0 (34.0–62.4) nmol/L. At mean age 19.1 months, n = 504, mean (SD) SLL was 31.7 (1.7) cm; CCL:L-ratio 0.62 (0.01). At 36.3 months, n = 956, mean SLL was 42.9 (2.0) cm; SH:H-ratio 0.56 (0.01). No participants had rickets. In adjusted analyses, 19-months-old boys had 0.1 cm shorter SLL (p = 0.009) and 0.1% higher CCL:L-ratio (p = 0.04) with every 10 nmol/L increase in cord 25OHD. Similar findings were seen for late pregnancy 25OHD. In the highest cord 25OHD quartile (>60.7 nmol/L), SLL was 0.8 cm shorter (95% C.I.: 1.36;-0.29, linear trend, p = 0.004), and CCL:L-ratio 0.8% higher (95% C.I. 8.0x10-05;0.01, linear trend, p = 0.01), compared to lowest quartile (<30.7 nmol/L). Similar associations with cord 25OHD were observed in 3-year-old boys. No consistent associations between 25OHD and anthropometrics were seen in girls at either age.ConclusionNo leg shortening was found with decreasing cord s-25OHD in a healthy population of infants. A small, yet significant inverse association between cord 25OHD and SLL in boys 1½-3 years warrants further investigations.

S-25OHD Is Associated With Hand Grip Strength and Myopathy at 5 Years in Girls: An Odense Child Cohort Study.

Severe vitamin D deficiency may lead to myopathy in adults. Little is known about vitamin D and muscle strength in children. To test whether hand grip strength (HGS) in 5-year-old children is associated with serum 25-hydroxyvitamin D (S-25OHD). Observational study in the population-based Odense Child Cohort, Denmark. At 5 years, anthropometrics, body fat percentage by skinfold measurements, HGS (n = 881), and S-25OHD2+3 (n = 499) were obtained. Mean (SD) HGS was higher for boys compared with girls [8.76 (1.76) vs 8.1 (1.64) kg, P < 0.001]. Mean (SD) 5-year S-25OHD was 70.7 (24.5) nmol/L. HGS was directly associated with height in girls and with weight (directly) and body fat percentage (inversely) in both sexes (P < 0.01 for all). In girls, 5-year S-25OHD was associated with HGS, adjusting for height, weight, and body fat percentage [β = 0.011 (95% CI: 0.004; 0.019), P = 0.003]. S-25OHD ≥75 nmol/L was associated with higher HGS compared with values <50 nmol/L [adjusted β = 0.783 (95% CI: 0.325; 1.241), P = 0.001]. The odds of having myopathy (HGS <10th percentile) were reduced by approximately 70% for S-25OHD ≥50 vs <50 nmol/L [adjusted OR: 0.310 (95% CI: 0.126; 0.762), P = 0.011]. No associations were seen for boys. Pregnancy or umbilical cord S-25OHD did not associate with 5-year HGS. Five-year S-25OHD was independently associated with HGS and myopathy in girls but not in boys. Muscle strength may be dependent on vitamin D status even in the higher range in preschool girls. The sex difference remains unexplained.

Cord serum25-hydroxyvitamin D is not associated with cranial anthropometrics in infants up to 6months of age. An Odense Child Cohort study.

Skull changes are poorly described in vitamin D insufficiency [serum 25-hydroxyvitamin D (s-25(OH)D) 25-50nmol/L]. We aimed to investigate factors associated with cranial anthropometrics in infants, especially s-25(OH)D. In infants 2.5-6months old from the Odense Child Cohort, associations between cord and pregnancy s-25(OH)D and anterior fontanel area (n=765), head circumference (HC, n=1776) and head shape (n=1527) were investigated along with other factors. Age was corrected for preterm birth. The mean (SD) s-25(OH)D in early pregnancy was 65.97 (21.33) nmol/L; late pregnancy 78.61 (27.18) nmol/L; and cord 47.1 (21.7) nmol/L. At median (IQR) age 3.7 (2.5-5.9) months, the fontanel area was 225 (0-1690) mm2, and mean (SD) HC was 41.5 (1.5) cm. Asymmetric/flat head shape was present in 846 infants (55.3%). No associations were found between cord, early or late pregnancy s-25(OH)D and any cranial measure by univariate or adjusted analysis. Among significant, independent associations in multivariate analysis, fontanel area was associated inversely with gestational age (GA); HC was associated directly with GA, maternal pre-pregnancy overweight and caesarean section and inversely with smoking; and asymmetrical head shape showed a novel association with male sex: adjusted OR=1.54 (95% CI 1.25; 1.89), p<0.001. Other associations with asymmetrical head shape included parity 3+, gestational age and maternal age 30+years (all protective). In conclusion, neither pregnancy nor cord s-25(OH)D was associated with fontanel size, HC or asymmetrical head shape despite a high prevalence of cord s-25(OH)D<50nmol/L. Lower GA was associated with larger fontanel size, lower HC and asymmetrical head shape, and boys more frequently had asymmetrical head shape, probably due to heavier heads.

S-25-hydroxyvitamin D and C3-epimers in pregnancy and infancy: An Odense Child Cohort study

BackgroundAnalysis of serum 25-hydroxyvitamin D (s-25(OH)D) may be complicated by the less active or in-active vitamin D metabolite C3-epi-25(OH)D3 (C3-epimer). We aimed to explore the relationship between s-C3-epimer and s-25(OH)D and other determinants and describe the longitudinal course of the C3-epimer fraction in paired mother-child samples. MethodS-25(OH)D and s-C3-epimer were estimated by liquid chromatography mass spectrometry in 290 mother-infant pairs from the population-based Odense Child Cohort. Longitudinal analyses were feasible in two subcohorts; B) early and late pregnancy, cord, three and 18months (n=132); and C) early and late pregnancy, delivery and cord (n=105). ResultsMean s-25(OH)D was 50.6–110.4nmol/L at the six time points. The mean C3-epimer fraction was 10.1% at three months, 1.1%–3.0% at the other time points. In multivariate analyses, the s-C3-epimer correlated with s-25(OH)D (all time points, p<0.001), and season, maternal and infant age and maternal vitamin D supplementation at some time points. The C3-epimer fraction fluctuated between adjacent time points. By cosinor analyses, a season-dependent sinusoidal pattern for s-25(OH)D and C3-epimer fraction was found and changes between adjacent time points depended on season (p<0.007 or trend). In early infancy, subtraction of the C3-epi-25(OH)D3 from total s-25(OH)D resulted in reclassification of 8% of the children by use of the 75nmol/L cut off for s-25(OH)D. ConlcusionThe s-C3-epimer was independently correlated to s-25(OH)D, season, maternal vitamin D supplementation, maternal and infant age. The C3-epimer fraction was only of clinical importance in early infancy, where it could lead to misclassification of the vitamin D status.